The advent of combinatorial chemistry has provided a platform for a wide variety of opportunities. The ability to produce large libraries of different compounds means that one can screen a large array of conformations, and charge distributions for their ability to bind to other compounds to act as agonists or antagonists, in binding to specific sites of a target protein, to investigate the conformation of a particular protein site, such as an enzymatic cleft or membrane channel protein, and the like.
The existence of combinatorial chemistry affords new opportunities towards new therapies for diseases for which prior drugs are inadequate or for which there are no present successful therapies. The presently available drugs are inadequate for a wide variety of reasons, in many cases, the pharmacokinetics of the drugs. Parenteral delivery in a bolus has many constraints on its efficacy. Since most drugs have serious side effects, one is constrained as to the upper dosage level. On the other hand, drugs may undergo enzymatic modification, oxidation, degradation in the liver, secretion, and the like, so that the lifetime of the drug will be limited by the various mechanisms which serve to diminish the effective level of the drug.
Drugs which have been approved for use with humans have already been shown to be generally safe at the prescribed dosage and effective. Therefore, there are substantial advantages in being able to modify these drugs, where their safety and efficacy are not unduly altered. In this way, the economies of dealing with known entities can be achieved, while at the same time increasing the available therapeutic opportunities.